title: Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy.
abstract: This review describes the changes that occur in circulating renin-angiotensin-aldosterone system (RAAS) components in human pregnancy. These changes depend on endocrine secretions from the ovary and possibly the placenta and decidua. Not only do these hormonal secretions directly contribute to the increase in RAAS levels, they also cause physiological changes within the cardiovascular system and the kidney, which, in turn, induce reflex release of renal renin. High levels of ANG II play a critical role in maintaining circulating blood volume, blood pressure, and uteroplacental blood flow through interactions with the ANG II type I receptor and through increased production of downstream peptides acting on a changing ANG receptor phenotype. The increase in ANG II early in gestation is driven by estrogen-induced increments in angiotensinogen (AGT) levels, so there cannot be negative feedback leading to reduced ANG II production. AGT can exist in various forms in terms of redox state or complexed with other proteins as polymers; these affect the ability of renin to cleave ANG I from AGT. Thus, during pregnancy the rate of ANG I production varies not only because levels of renin change in response to homeostatic demand but also because AGT changes not only in concentration but in form. Activation of the circulating and intrarenal RAASs is essential for normal pregnancy outcome subserving the increased demand for salt and, hence, water during pregnancy. Thus, the complex integration of the secretions and actions of the circulating maternal renin-angiotensin system in pregnancy plays a key role in pregnancy outcome.
authors.affiliation: School of Biomedical Sciences and Pharmacy and Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Eugenie R
authors.initials: ER
authors.lastname: Lumbers
authors.forename: Kirsty G
authors.initials: KG
authors.lastname: Pringle
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000809:Angiotensins / Q000378:metabolism*; D005260:Female; D006801:Humans; D011247:Pregnancy / Q000502:physiology*; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D000809:Angiotensins; D000450:Aldosterone; D012083:Renin
keywords: circulation; fluid and electrolyte balance; pregnancy; renal function; renin-angiotensin-aldosterone system